Stroke is the 3rd leading cause of death and number one cause of adult disability in the United States. The primary goal of ischemic stroke treatment is quickly restoring blood perfusion. However, studies have shown that this return of blood flow, while necessary to bettering patient outcome, can cause damage to local tissue. Hypothermia has been shown to decrease this "reperfusion injury". The overall goal of this proposed research is to use therapeutic hypothermia to augment the tissue salvage capabilities of existing mechanical clot removal devices that restore perfusion by reducing reperfusion injury. Our proposed device is a cooling guide catheter which will function identically to conventional guide catheters but with blood cooling capabilities to save ischemic tissue at risk of reperfusion injury. Specific Aims: 1.) Design a cooling guide catheter that can be used with existing mechanical clot removal devices and that can quickly reduce target tissue temperatures, 2.) characterize device thermal-fluid performance in an in vitro brain model, and 3.) demonstrate that the cooling catheter can safely and effectively decrease target tissue temperature in a small animal pilot study. To achieve these aims the following will be performed: thermal-fluid modeling, design input requirements and feasibility points, development of prototype designs, coolant pressure-flow behavior characterization, in vitro thermal-fluid performance testing for each prototype in system that mimics intracranial blood flow, and in vivo testing demonstrating that rapid localized tissue cooling is feasible and that the catheter is hemocompatibile with no significant damage to vessels or tissue. Relevance: The technological innovation of combining stroke treatment therapies - mechanical clot removal and reperfusion hypothermia - may yield synergistic benefits, resulting in reduced infarct size and improved neurological outcomes compared to outcomes using either technology separately. If fast and safe cooling is shown feasible in Phase I, Phase II would investigate efficacy using an animal stroke model. PUBLIC HEALTH RELEVANCE: Stroke is the 3rd leading cause of death and number one cause of adult disability in the United States. For stroke treatment, quickly restoring blood flow has been shown to improve outcome, although some experts have found reperfusion injury mitigates these benefits. FocalCool, LLC seeks to combine two technologies, thrombectomy and therapeutic hypothermia using a novel cooling guide catheter potentially maximizing the benefit of blood flow restoration while minimizing damaging effects of reperfusion injury.